Isoprenaline-induced changes in type I inhibitor activity as an index of beta-adrenergic receptor subsensitivity

Isoprenaline produced a dose-dependent decrease in the activity of an endogenous, specific inhibitor of cAMP-dependent protein kinase (type I inhibitor) in rat hippocampus, brain stem and pineal gland. Prolonged, 21-days treatment with some antidepressant (imipramine, nomifensin and mianserin) markedly reduced the response of the type I inhibitor activity to isoprenaline. To obtain the significant decrease of the type I inhibitor activity, five times higher dose of isoprenaline had to be used in these animals than in control rats. Mianserin is known to produce a decrease of the activity of adenylate cyclase coupled to beta-adrenergic receptors without changing the number of receptor binding sites. In the present study we have shown that also mianserin after prolonged treatment produces subsensitivity of beta-adrenergic receptors when measured by the response of the type I inhibitor activity to isoprenaline. Single doses of imipramine, nomifensin and mianserin did not change the isoprenaline-induced decrease of the type I inhibitor activity. It seems that the isoprenaline-induced decreased of the type I inhibitor activity can be used as an index of beta-adrenergic receptor reactivity.